The basic purpose of this project is to clarify the role of silicon deficiency in the etiology of atherosclerosis, and the involvement of silicon in the prevention of that disease. Silicon, shown to be essential for normal growth and development, acts as a cross-linking agent in connective tissue. High levels are found in arterial walls. The role of silicon in cholesterol absorption and metabolism, lipid transport, etc. will be investigated. Silicon deficiencies in rats maintained in a trace element controlled environment system will be studied with respect to atherosclerosis and tolerance toward dietary cholesterol. The biological potency of organic silicic acid derivatives is being assayed to determine chemical properties which underlie biological activity. Naturally occurring organic silicon derivatives from connective tissue are being isolated, chemically characterized, and subsequently synthesized. Preventive and therapeutic trials will be carried out with these substances in animal models of atherosclerosis. The final aim is to make silicon compounds available for human trials.